Enhanced meniscal repair by overexpression of hIGF-1 in a full-thickness model

Clin Orthop Relat Res. 2009 Dec;467(12):3165-74. doi: 10.1007/s11999-009-0921-8. Epub 2009 Jun 13.

Abstract

The importance of the menisci to the well-being of the normal knee is well-documented. However, there is no ideal repair or reconstructive approach for damaged menisci. Gene therapy provides one promising alternative strategy, especially when combined with injectable tissue engineering to achieve minimally invasive clinical application. We asked whether the introduction of human insulin-like growth factor 1 (hIGF-1) gene could improve the repair of full-thickness meniscal defects. We created full-thickness meniscal defects in the "white area" of the anterior horn in 48 goats. Bone marrow stromal cells with the transfection of hIGF-1 gene and injectable calcium alginate gel were mixed together to repair the defects; three control groups included cells without transfection, gel without cells, and defects left empty. After 4, 8, and 16 weeks, the animals were euthanized and the excised defects were examined by macroscopic assessment, histological analysis, electron microscopy, proteoglycan determination, and MRI. Sixteen weeks after surgery the repaired meniscal defects were filled with white tissue similar to that in normal meniscal fibrocartilage. The repair tissue was composed of cells embedded within matrix that filled the spaces of the fibers. The proteoglycan content in the gene-enhanced tissue engineering group was higher than those in the control groups, and less than that in the normal meniscus. The results suggest full-thickness meniscal defects in regions without blood supply can be reconstructed with hIGF-1-enhanced injectable tissue engineering.

MeSH terms

  • Alginates / administration & dosage
  • Animals
  • Bone Marrow Transplantation
  • Cells, Cultured
  • Chondrogenesis*
  • Disease Models, Animal
  • Gels
  • Genetic Therapy / methods*
  • Glucuronic Acid / administration & dosage
  • Goats
  • Hexuronic Acids / administration & dosage
  • Humans
  • Injections, Intra-Articular
  • Insulin-Like Growth Factor I / biosynthesis*
  • Insulin-Like Growth Factor I / genetics
  • Knee Injuries / genetics
  • Knee Injuries / metabolism
  • Knee Injuries / pathology
  • Knee Injuries / surgery
  • Knee Injuries / therapy*
  • Liposomes
  • Magnetic Resonance Imaging
  • Male
  • Menisci, Tibial / metabolism*
  • Menisci, Tibial / pathology
  • Microscopy, Electron, Transmission
  • Proteoglycans / metabolism
  • Stromal Cells / metabolism
  • Stromal Cells / transplantation*
  • Time Factors
  • Tissue Engineering*
  • Transfection

Substances

  • Alginates
  • Gels
  • Hexuronic Acids
  • Liposomes
  • Proteoglycans
  • Insulin-Like Growth Factor I
  • Glucuronic Acid